Why clinical translation cannot succeed without failure

eLife

Volumn 4, Issue NOVEMBER2015, 2015, Pages 1-5

  London, Alex John ^a   Kimmelman, Jonathan ^b  

^a CARNEGIE MELLON UNIVERSITY   (United States)

^b MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; COST; DRUG DEVELOPMENT; INFORMATION PROCESSING; KNOWLEDGE; MEDICAL ETHICS; MEDICAL RESEARCH; PUBLISHING; SAMPLE SIZE; STUDY DESIGN; ANIMAL; CLINICAL TRIAL (TOPIC); DISEASE MODEL; HUMAN; PRECLINICAL STUDY; PROCEDURES; TRANSLATIONAL RESEARCH; TREATMENT FAILURE;

ANIMALS; CLINICAL TRIALS AS TOPIC; DISEASE MODELS, ANIMAL; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; HUMANS; TRANSLATIONAL MEDICAL RESEARCH; TREATMENT FAILURE;

EID: 84949951947     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.12844     Document Type: Article

References (25)

1. Button KS, Ioannidis JP, Mokrysz C, Nosek BA, Flint J, Robinson ES, Munafò MR. 2013. Power failure: why small sample size undermines the reliability of neuroscience. Nature Reviews Neuroscience 14:365–378. doi: 10.1038/nrn3475.
2. Collins FS, Tabak LA. 2014. NIH plans to enhance reproducibility. Nature 505:612–613. doi: 10.1038/505612a.
3. Collins FS. 2011. Reengineering translational science: the time is right. Science Translational Medicine 3:90cm 17. doi: 10.1126/scitranslmed.3002747.
4. Conti RM, Bernstein AC, Villaflor VM, Schilsky RL, Rosenthal MB, Bach PB. 2013. Prevalence of off-label use and spending in 2010 among patent-protected chemotherapies in a population-based cohort of medical oncologists. Journal of Clinical Oncology 31:1134–1139. doi: 10.1200/JCO.2012.42.7252.
5. Cyranoski D. 2013. Japan to offer fast-track approval path for stem cell therapies. Nature Medicine 19:510. doi: 10.1038/nm0513-510.
6. Decullier E, Chan AW, Chapuis F. 2009. Inadequate dissemination of phase I trials: a retrospective cohort study. PLOS Medicine 6:e1000034. doi: 10.1371/journal.pmed.1000034.
7. Djulbegovic B, Kumar A, Glasziou P, Miladinovic B, Chalmers I. 2013. Trial unpredictability yields predictable therapy gains. Nature 500:395–396. doi: 10.1038/500395a.
8. Freedman B. 1987. Equipoise and the ethics of clinical research. N Engl J Med 317:141–145.
9. Freeman GA, Kimmelman J. 2012. Publication and reporting conduct for pharmacodynamic analyses of tumor tissue in early phase oncology trials. Clinical Cancer Research 18:6478–6484. doi: 10.1158/1078-0432.CCR-12-1384.
10. Green AK, Reeder-Hayes KE, Corty RW, Basch E, Milowsky MI, Dusetzina SB, Bennett AV, Wood WA. 2015. The project data sphere initiative: accelerating cancer research by sharing data. The Oncologist 20:464-e20. doi: 10.1634/theoncologist.2014-0431.
11. Greenberg SA. 2009. How citation distortions create unfounded authority: analysis of a citation network. BMJ 339:b2680. doi: 10.1136/bmj.b2680.
12. Hakala A, Kimmelman J, Carlisle B, Freeman G, Fergusson D. 2015. Accessibility of trial reports for drugs stalling in development: a systematic assessment of registered trials. BMJ 350:h1116. doi: 10.1136/bmj.h1116.
13. Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. 2014. Clinical development success rates for investigational drugs. Nature Biotechnology 32:40–51. doi: 10.1038/nbt.2786.
14. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. 2001. Replication validity of genetic association studies. Nature Genetics 29:306–309. doi: 10.1038/ng749.
15. Khozin S, Blumenthal GM, Zhang L, Tang S, Brower M, Fox E, Helms W, Leong R, Song P, Pan Y, et al. 2015. FDA approval: ceritinib for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer. Clinical Cancer Research 21:2436–2439. doi: 10.1158/1078-0432.CCR-14-3157.
16. Kimmelman J, London AJ. 2015. The structure of clinical translation: efficiency, information, and ethics. Hastings Center Report 5:27–39. doi: 10.1002/hast.433.
17. Kimmelman J, Mogil JS, Dirnagl U. 2014. Distinguishing between exploratory and confirmatory preclinical research will improve translation. PLOS Biology 12: e1001863. doi: 10.1371/journal.pbio.1001863.
18. Kimmelman J. 2012. A theoretical framework for early human studies: uncertainty, intervention ensembles, and boundaries. Trials 13:173. doi: 10.1186/1745-6215-13-173.
19. Kola I, Landis J. 2004. Can the pharmaceutical industry reduce attrition rates? Nature Reviews Drug Discovery 3:711–715. doi: 10.1038/nrd1470.
20. London A. 2007. Clinical equipoise: foundational requirement or fundamental error. In: Steinbock B, editor. The Oxford Handbook of Bioethics. Oxford: Oxford University Press. p. 571–596.
21. Peart KN. 2015. Yale YODA project announces first availability of medical device trial data. Yale News. Available at: http://news.yale.edu/2015/01/14/yaleyoda-project-announces-first-availability-medicaldevice-trial-data.
22. Rettig RA. 2007. False Hope: Bone Marrow Transplantation for Breast Cancer. Oxford: Oxford University Press.
23. Schmidt C. 2011. How do you tell whether a breast cancer is HER2 positive? Ongoing studies keep debate in high gear. Journal of the National Cancer Institute 103:87–89. doi: 10.1093/jnci/djq557.
24. Smyth RM, Kirkham JJ, Jacoby A, Altman DG, Gamble C, Williamson PR. 2011. Frequency and reasons for outcome reporting bias in clinical trials: interviews with trialists. BMJ 342:c7153. doi: 10.1136/bmj.c7153.
25. Yusuf S, Collins R, Peto R. 1984. Why do we need some large, simple randomized trials? Statistics in Medicine 3:409–422. doi: 10.1002/sim.4780030421.